On 7 Feb 2002 at 10:41:21, "panteha khalili" (parsiwa.-at-.hotmail.com) sent the message

The following message was posted to: PharmPK

Dear readers,In the cases of enterohepatic recirculation as manifested in thepresence of second hump in the blood concentration-time curves, howshould one measure elimination half-life, ie. which line's slope shouldbe considered?Any suggestions would be greatly appreciated.

[Interesting question - I would try to set-up a suitable compartmentalmodel with a delayed bile emptying - seehttp://www.boomer.org/manual/EG/ehrc0/ehrc.html for a model and Boomer.BAT files (this must have been a question asked earlier ;-) - db]

On 7 Feb 2002 at 17:39:30, "Stephen Duffull" (sduffull.at.pharmacy.uq.edu.au) sent the message

The following message was posted to: PharmPK

Dear Panteha

>In the cases of enterohepatic recirculation as manifested in thepresence of second hump in the blood concentration-time curves, howshould one measure elimination half-life, ie. which line's slope shouldbe considered?

I am analysing data that seems to display enterohepatic circulation atthe moment. Basically the only way you can compute 'half-life' is fromthe compartment model - so you will have to model it. The model shown byDavid Bourne (http://www.boomer.org/manual/EG/ehrc0/ehrc.html) is theusual setup - although I suspect 'kg' and 'k_empty' would not beglobally identifiable since the RLS would be the gallbladder emptyingdelay (is this your understanding David?). You can however estimate thefraction of drug that undergoes enterohepatic recirculation and thedelay in gallbladder emptying.

[Yes, Steve I think we are on the same page. I would be inclined to setk_empty to some arbitrarily high (fixed) number and adjust emptyingtime. If you have some information about amount excreted versus themetabolism steps kg shouldn't be too much of a problem. Identifiabilitycould be a challenge with just plasma data. I wonder if the relativepeak sizes would give enough information to determine ke and kg - thiswould be related to the fraction term Steve has above. k_empty is alwaysgoing to be tough if you want ka. Maybe I need to do a 'sensitivity'analysis with a .BAT file - db]

On 8 Feb 2002 at 14:39:55, "He, Yan-Ling" (YHE.at.PARTNERS.ORG) sent the message

The following message was posted to: PharmPK

I completely agree with Dr. Aarons. To do a precise modelng for a drugwith significant EHC, you may have to evalaute the drug concentrationvs. time profile in bile in addition to the blood drugconcentration-time profile. If you are only interestd in evaluating thedrug disposition, mean residence time (MRT) in the body rather thanelimination half-life would give you a better idea, becasue thisparameter is a statistical parameter that characterizes the "shape" ofthe drug concentration-time profile.

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